Mechanisms of Disease: Carcinogenesis in Barrett's Esophagus

Navtej S Buttar; Kenneth K Wang


Nat Clin Pract Gastroenterol Hepatol. 2004;1(2) 

In This Article

Diet, Life Style and Obesity

In Western countries in the past two decades, obesity has reached epidemic proportions in parallel with an increase in the development of esophageal adenocarcinoma. Obesity, the increased incidence of which is mainly due to consumption of high-calorie diets and increased sedentary behavior,[25,26,27,28] has emerged as a risk factor for esophageal adenocarcinoma, as has the modest decrease in dietary intake of fresh fruits and vegetables.[25,26] In a multicenter population-based case-control study in the US, it was reported that having a body mass index (BMI) in the highest quartile was associated with a fourfold increase in the risk of developing esophageal adenocarcinoma compared with having a BMI in the lowest quartile.[26] In Sweden, individuals in the highest BMI quartile had an almost eightfold increased risk of esophageal adenocarcinoma compared with individuals in the lowest quartile.[27] Epidemiological studies also suggest that there is an increased risk of developing esophageal adenocarcinoma from higher consumption of dietary cholesterol and protein. A decrease in the risk of esophageal adenocarcinoma has been noted with consumption of fiber, vitamins C, B6, E, folate and beta-carotene.[25,26,27,28]

Obesity and lack of physical activity increase insulin resistance and are associated with increased circulating levels of many steroid hormones as well as insulin-like growth factor-1 (IGF-1).[28] Increased expression of the IGF-1 receptor (IGF1-R) is associated with progression of neoplasia in Barrett's esophagus.[29] Binding of increased levels of circulating IGF-1 to IGF1-R could transduce signals through several intracellular pathways, stimulating the malignant transformation of various epithelial and mesenchymal cells, and also protecting these cells against apoptosis.[30]

Possible mechanistic links between obesity, dietary habits and the development of esophageal cancer need to be explored, including the antioxidant effect of vitamins, which might account for their cancer-preventive effects.


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